Kromosom, Gen, DNA

DNA merupakan polimer asam nukleat yang tersusun secara sistematis dan merupakan pembawa informasi genetic yang diturunkan pada jasad keturunannya. Informasi genetic ini disusun dalam bentuk kodon berupa tiga pasang basa nukleotida dan menentukan struktur, bentuk maupun fisiologi suatu jasad.

Struktur molekul DNA pertama kali diungkapkan oleh james Watson dan Francis Crick pada tahun 1953 berdasarkan atas foto difraksi sinar X yang dibuat oleh Rosalind Franklin dan Maurice Wilkins. Berdasarkan atas data kimia fisik, Watson dan Crick membuat model struktur DNA yang disebut untai ganda (double helix). Untai ganda DNA tersusun oleh dua rantai polinukleotida yang berpilin. Kedua rantai memiliki orientasi yang berlawanan (antiparalel). Rantai yang satu mempunyai orientasi dari ‘5-3’ sedangkan rantai yang lain berorientasi 3’-5’. Kedua rantai direkatkan oleh ikatan hydrogen antar basa-basanya. A berpasangan dengan T membentuk dua ikatan hydrogen sedangkan C berpasangan dengan G membentuk tiga ikatan Hidrogen. Spesifisitas semacam ini disebut sebagai komplementaritas.. Proporsi basa A dan T serta C dan Gselalu sama sehingga komposisi DNA dapat dinyatakan dengan kandungan G + C yang berkisar 26% sampai 74%. Hal ini dikenal dengan hukum Chargaff.

Pengemasan DNA pada Sel eukaryote

DNA utama pada eukaryote dikemas dengan system efisien dan kompak . DNA dikemas dengan menggunakan protein histon yang terdiri dari lima macam yaitu H1, H2A, H2B, H3, dan H4. Protein histon digunakan untk menggulung molekul DNA.Satu kompleks DNA dan histon disebut dengan Nukleosom. Dalam satu kompleks histon tersebut DNA digulung kurang lebih 2 Kali. Antara nukleosom satu dengan yang lain dihubungkan oleh molekul DNA yang tidak berikatan dengan histon sehingga disebut dengan DNA penghubung (linker DNA). Pada waktu gen sedang aktif ditranskriapsikan atau pada saat terjadinya replikasi DNA, DNA nukleosom akan menjadi lebih sensitive terhadap nuclease, sehingga diindikasikan adanya penguraian nukleosom. Rangkaian nukleosom membentuk struktur yang disebut dengan Kromatin. Kromatin merupakan struktur kompleks yang terdiri atas DNA, protein dan RNA 9kurang dari 10%). Pada aras struktur yang lebih tinggi kromatin membentuk struktur yang disebut solenoid (struktur pilinan nukleosom). Struktur solenoid yang terkondensasi secara kompak membentuk struktur khas kromosom.

Struktur Kromosom terdiri atas

1. Lengan Kromosom : terdiri dari dua bagian p arm (lengan pendek) dan q arm (lengan panjang). Lengan kromosom mengandung rangkaian gen.

2. Sentromer : bagian tengah kromosom yang berfungsi dalam distribusi kromosom pada waktu terjadinya pembelahan sel

3. Telomere : bagian ujung kromosom.

Sentromer berikatan dengan suatu protein yang disebut dengan kinetokor yang berikatan dengan protein yang disebut dengan benang gelendong yang menarik kromosom ke arah kutub-kutub yang berlawanan pada waktu terjadinya pembelahan sel.

Kromosom dapat dicat dengan cat Giemsa. Bagian yang tidak terlalu rapat pengemasannya disebut eukromatin yang mengandung gen-gen yang ekspresinya diperlukan dalam pemeliharaan aktivitas fisiologis sel, misalnya untuk produksi energy seluler. Bagian yang lebih rapat disebut dengan heterokromatin. Pada jasad tingkat tinggi kromosom dibedakan atas kromosom tubuh (autosom) dan kromosom seks (X dan Y).

Replikasi DNA

Replikasi DNA merupakan proses yang kompleks dan dibantu oleh beberapa enzim dan dimulai pada suatu titik yang disebut Origin Of replication (ORI) dari ORI replikasi akan berlangsung ke dua arah (bidireksional) dan dibantu oleh beberapa enzim dan protein antara lain helikase, SSB, Primase, DNA polymerase, Ligase dan telomerase.

Proses Replikasi

Replikasi diawali dengan pemutusan ikatan-ikatan hydrogen oleh enzim helikase sehingga kedua rantai terpisah. Kedua rantai yang terpisah diikat oleh SSB untuk mencegah terjadinya penggabungan kembali kedua rantai. Selanjutnya primase akan mensintesis oligonukleotida (berupa RNA) disebut primer, primer menyediakan gugus 3-OH yang dibutuhkan oleh DNA polymerase untuk meperpanjang rantai DNA. Tahap selanjutnya adalah pemanjangangan rantai DNA oleh DNA polymerase. Proses pemanjangan hanya berlangsung dari 5’ ke 3’.

DNA yang disintesis se arah dengan pembukaan double heliks akan menghasilkan rantai yang kontinu disebut dengan leading strand sedangkan rantai yang berlawanan dengan arah garpu replikasi akan menghasilkan rantai fragmen-fragmen DNA pendek disebut dengan fragmen Okazaki yang kemudian akan disatukan dengan bantuan enzim ligase, rantai ini disebut dengan lagging strand.

Sintesis Protein

Gen dan protein merupakan dua hal yang tidak dapat dipisahkan. Gen merupakan segmen DNA yang terdapat dalam kromosom. Produk seluler yang dikodekan oleh gen sebagian besar adalah protein.

RNA adalah suatu asam nukleat yang membantu dalam mentranskripsi dan menerjemahkan informasi genetic DNA ke dalam bentuk asam amino. Terdapat 3 RNA yang berperan dalam proses ini yaitu: 1) mRNA, 2)tRNA dan 3) rRNA.

Tahapan Sintesis Protein

Trankripsi

Enzim yang berperan dalam proses transkripsi adlah RNA polymerase yang bergerak sepanjang gen dari promotornya hingga terminator. RNA polymerase memasangkan molekul nukleotida pada rantai RNA sehingga sesuai dengan untaian template.

1) Setelah mengikat promoter RNA polymerase melepaskan rantai ganda DNA dan menginisiasi sintesis RNA pada titik awal untaian template. Urutan nukleotida promoter menentukan kerja RNA polymerase

2) RNA polymerase bekerja downstream berawal dari promoter dan mengalami elongasi dari arah 5’ ke 3’

3) Pada saat RNA polymerase menerjemahkan terminator, sehingga proses berhenti dan RNA polymerase melepaskan diri dari DNA, mRNA terbentuk.

Translasi

mRNA kemudian meninggalkan intisel, bergerak ke ribosom dan berikatan dengan subunit kecil. tRNA membawa asam amino ke mRNA Antikodon tRNA yang sesuai akan berpasangan dengan

mRNA. Subunit besar dan kecil dari ribosom bergabung dan tRNA berikatan dengan subunit besar ribosom. Subunit besar ribosom kemudian mengkatalis proses pembentukan ikatan peptide antara asam-asam amino yang dibawa oleh tRNA. Pada saat asam amino baru bergabung dengan asam amino yang telah ada sebelumnya, tRNA melepaskan diri dari subunit besar ribosom dan tRNA yang membawa asam amino baru menggantikan tRNA tersebut. Proses ini berlanjut hingga kodon stop. Pada akhir proses ini, mRNA dan protein yang selesai terbentuk meninggalkan ribosom.

HUBUNGAN ANTARA AUTISME DAN FRAGILE X SYNDROME

Jenny L. Demark

Terdapat beberapa bukti dalam beberapa literature yang menyatakan bahwa orang dengan kelainan fragile X syndrome (FraX) memiliki resiko yang lebih tinggi mengalami autism. Walaupun masih belum jelas bagaimana atau mengapa dua kelainan ini berhubungan. Bahkan jika orang dengan kelainan fragile X tidak sepenuhnya didiagnosa memiliki criteria autism mereka tetap memiliki beberapa sifat yang tipikal pada penderita autis seperti gerakan tangan penderita autis, kemampuan komunikasi yang abnormal, dan sulit melakukan kontak mata dengan orang lain. Jurnal ini membahas baik kelainan autism dan FraX, serta review pada perilaku, genetic dan penelitian neuroanatomical tentang hubungan keduanya.

AUTISM

Autisme adalah gangguan perkembangan mental dengan beberapa gejala berupa gangguan kemampuan social, keterlambatan atau ketidak adaannya kemampuan berbicara, dan adanya gerakan-gerakan berulang (American Psychiatric Association, 1994). Kebanyakan orang yang menderita autism memiliki gangguan perkembangan, walaupun sekitar 20% penderita autism memiliki IQ yang normal (Klinger & G.Dowson,1996)

Beberapa penelitian telah dilakukan untuk menemukan neurochemical spesifik dan atau kekurangan pada struktur neuroanatomical pada penderita autism tetapi hasilnya beragam. Telah dilaporkan bahwa kerusakan pada serebral (Courchesnes,Townsend, & Saitoh, 1994) dan terdapat beberapa bukti adanya peningkatan sel di daerah hippocampus otak. Spekulasi lainnya menyebutkan kesalahan pada 4 mekanisme neurofungsional yangg berbeda meningkatkan kemungkinan menderita autism.(Waterhouse, Fein &Modahl, 1996)

Telah diketahui bahwa autism memiliki dasar genetic. Penelitian yang berbeda telah memeriksa keluarga yang mengalami autism dan menemukan, rata-rata bahwa saudara dekat memiliki kemungkinan 3-5% mengalami autis secara substansial lebih tinggi perkiraan untuk populasi umumnya (5-10 dalam 10.000 penduduk). Sebuah kemungkinan model non-mendelian dari autrisme adalah penurunan sifat multifaktorial dimana sejumlah besar gen dan atau factor lingkungan berkontribusi dalam perkembangan kelainan ini.

FRAGILE X SYNDROME

Fragile X syndrome bentuk ketidak mampuan perkembangan yang diturunkan. Hal ini dikarenakan perluasan dari sebuah daerah triplet nukleotida berulang di gen Fragile X mental retardation 1 (FMR 1) yang ditemukan pada kromosom X sehingga menimbulkan bagian yang rapuh. Daerah Triplet nukleotida yang berulang pada FMR1 terdiri dari sitosin-guanin-guanin (CGG) yang sekuensnya berulang lagi dan lagi. Dalam bentuk umumnya gen FMR1 mengandung 5 sampai 50 pengulangan basa-basa CGG, namun dalam Fragile X syndrome

pengulangan ini dapat terjadi hingga ratusan bahkan ribuan kali (ebehart & Warren,1996) Sehingga poroduct FMR1 yaitu Fragile X Mental Retardation protein (FMRP) tidak diproduksi, protein ini berlimpah pada neuron hippocampus dan otak besar pada orang-orang normal (orang-orang yang tidak mengalami kelainan). Bukti terbaru menyebutkan kemungkinan gen ini memainkan peranan yang penting dalam regulasi sintesis protein dalam respon aktivitas sinaptik (Feng,et all 1997). FMRP kemungkinan memiliki fungsi yang berbeda pada bagian lain dari perkembangan otak (C. Feinstein, 1997)

Stable Allele

Unstable allele

Premutation

Expansion to full Mutation

Abnormal methylation of FMR1 gene

Absence of FMRP

(CGG)n

n<45

55> n < 200

n>200

NO TRANSCRIPTION = NO FMR1 PROTEIN

Didalam keluarga, biasanya kelainan ini diturunkan pada generasi oleh wanita. Wanita yang membawa gen ini seringkali memiliki bentuk pre-mutasi dari gen FMR1 yang diperluas pada populasi normal. Tetapi tetap memproduksi FMRP (Fu et al, 1991). Wanita yang membawa gen pre-mutasi diperkirakan memiliki fungsi intelektual normal, tetapi memiliki resiko cenderung mengalami kelainan. Pria yang membawa gen pre-mutasi atau gen yang termutasi penuh cenderung menurunkan sifat gen pre-mutasi pada anak perempuannya, tetapi pada umumnya cucu akan mendapatkan gen yang termutasi secara penuh. Unuk pria yang mengalami gen mutasi penuh memiliki tingkat gangguan perkembangan yang berbeda-beda(Hagerman, et al, 1989)

Seseorang yang mengalami Fragile X syndrome cenderung memiliki level intelektual dan kebanyakan sifat mereka analog dengan penderita autism. Kebanyakan laki-laki pra-pubertas menunjukkan sifat hiperaktif, mengepak-ngepakkan tangan (hand flapping), tuli dan cenderung menghindari kontak mata dengan orang lain.

Hubungan Autisme dan Fragile X Syndrome

Penelitian Rogers dkk dengan sampel anak yang menderita Fragile X syndrome ( berumur kurang dari 4 tahun) cendeerung memiliki sifat autis dan memperkirakan hal ini kemungkinan karena umur mereka yang relative muda dan level perkembangan.

Kesamaan Antara Autisme dan Fragile X syndrome

Penderita autism dan fragile syndrome cenderung memiliki kesamaan perilaku. Seperti kurangnya respon saat diajak bersosialisasi, gangguan dalam berbicara, seringkali menggigit tangan, hand flapping, perubahan mood yang seringkali terjadi.

Perbedaan Antara Autisme dan fragile X syndrome

Dalam penelitian yang dilakukan oleh Madison, dkk 1989 Seseorang dengan kelainan autism memilik kemampuan yang lebih baik dalam pengerjaan tugas sementara penderita fragile x syndrome memiliki kemampuan berbicara yg lbh baik. Anak penderita autism cenderung sulit bersosialisasi sedangkan penderita fragile x syndrome cenderung sulit melakukan kontak mata.

Fragile X Syndrome Testing

1. Carrier testing- Keluarga dengan sejarah penyakit fragile X- Undiagnosed mental retardation

- Development delay or- Autism

2. Prenata diagnosisWhen the mother is a known carrier of fragile X (permutation or full mutation)

Fragile X syndrome

1. Features• Fragile X syndrome is the most common known inherited cause of intellectual disability and it has a wide variety of presentations. It is the second most common genetic cause of intellectual disability (Down syndrome is the most frequent).• Intellectual problems can vary from mild learning difficulties through to severe intellectual disability.• Emotional and behavioural problems may be present.• Females show varying degrees of the condition.• Early diagnosis can facilitate strategies that will enable individuals to achieve their maximum potential

a) Males with a full mutation(see ‘Genetics’ below)Typical features may not always be present, and may vary in severity.• Developmental delay: > Intellectual disability (100% of males) > Speech delay > Fine and gross motor delay

> Co-ordination difficulties > Hypotonia• Behavioural or emotional problems: > Attention-deficit disorders with or without hyperactivity > Speech disturbances including variable pitch, perseverative speech (repetition of word or phrase) and cluttering (rapid speech with repetitions and tangential remarks) > Autistic-like features, eg hand flapping and biting, gaze aversion, repetitive speech mimicry (echolalia) and preoccupation with objects > Sensory defensiveness (aversion to touch, loud noises, bright lights and strong smells) > Hyperarousal or anxiety > Mood instability with aggression and depression, especially in post-pubertal male• Medical conditions: > Up to 20% have epilepsy > Mitral valve prolapse > Recurrent ear infections > Eye problems, eg strabismus • Physical characteristics (may be subtle in childhood) > Large prominent ears > Long face > Large testicles > High, broad forehead > High arched palate > Connective tissue problems, eg: — Flat feet — Loose joints — Scoliosis

Females with a full mutation(see ‘Genetics’ below)• Around 60% of females with a full mutation have cognitive deficiencies with IQ in borderline (70-84) or mild disability range.• Females may also present with hyperactivity or a shy personality and some will present with selective mutism.• Females may also have the emotional and behavioural characteristics seen in affected males.• Generally speaking, affected females have a milder phenotype than affected males. Individuals with a premutation(see ‘Genetics’ below)• Premature ovarian failure > Female premutation carriers have approximately 20% risk of developing premature ovarian failure (menopause before the age of 40 years).• Fragile X tremor/ataxia syndrome (FXTAS)

> FXTAS is a progressive neurological disorder that usually starts after 50 years of age. It is characterised by intention tremor, cerebellar ataxia, Parkinsonism, peripheral neuropathy and dementia. > Both male and female premutation carriers may develop FXTAS. > The risk increases with age and in males is approximately 50% by age 79 years. Female premutation carriers are less likely to develop FXTAS; the risk is not quantifiable at this time.At-risk individuals• Individuals of either sex with: > Intellectual disability > Developmental delay > Autistic-like characteristics > Learning disabilities of unknown cause, including borderline cases > A family history of fragile X syndrome or relatives of a person with developmental delay of unknown cause. > A previous fragile X cytogenetic test result that was inconclusive• Consider offering fragile X DNA testing to: > All individuals at risk. > Adults (>50 years of age) who present with unexplained ataxia and/or intention tremor, Parkinsonism and dementia. > Preconceptionally or during pregnancy to any woman with a family history of fragile X syndrome or intellectual disability of unknown cause or a family history of premature ovarian failure. > Offer prenatal testing to females who are known to have a fragile X premutation or full mutation (see ‘Genetics’ below for details). Where the cause of intellectual disability has not been determined in the affected member(s) in the family, prenatal testing should be discussed and may be offered concurrently with testing of family members if time allows.

Genetics• Fragile X syndrome follows an X-linked pattern of inheritance. • However, due to the type of genetic alteration involved, the pattern of X-linked inheritance is atypical.• It is caused by a mutation in a gene on the X chromosome (the FMR1 gene: fragile X mental retardation 1). The FMR1 gene codes for a protein, FMRP, which is thought to be necessary for normal neurological functioning.• Fragile X syndrome results from an increase in the number of copies of a tri-nucleotide sequence within the gene (see Table 1). Most people have between 6 and 54 repeats, with an average of 30. Copy numbers between 55 and 200 or 230 (depending on how it is reported by the laboratory) are said to be ‘premutations’ and copy numbers of 200 or 230 and above are said to be ‘full mutations’. Genes with premutations and full mutations contain an expansion. Full mutations cause FMRP to be switched off, resulting in an individual having fragile X syndrome.

Inheritance pattern• The size of the expansion in the FMR1 gene is unstable and can change through generations. Both men and women with an expansion may pass it on to their children: > Mother to child transmission is unstable, and the expansion may increase in size > Mothers of affected males carry either a premutation or a full mutation > Father to daughter transmission is stable within a small variation for premutations; that is, the expansion will not increase to a full mutation > There is limited data on men with full mutations; however, it appears that daughters usually inherit a premutation from their affected fathers• Women who are carriers of a premutation or a full mutation have a 50% chance of passing it on to each of their children.• The risk of a female premutation carrier having a child with the full mutation is related to the size of her premutation.• Men pass a premutation or a full mutation on to all their daughters but to none of their sons, as the sons receive only their father’s Y chromosome.

A male diagnosed with fragile X syndrome could have inherited this from:

> A mother with a full mutation OR > A mother with a premutation• Family studies are likely to identify individuals with premutations and may identify individuals with full mutations. Genetic counselling is important and allows families to make informed decisions about family planning (see Contacts, support and testing).• It is difficult to distinguish between a normal version of the gene and a small premutation.• The number of repeats of an intermediate size (so called ‘grey zone’ in the upper end of normal range) can change into a premutation when passed on to children. Prevalence• Approximately 1 in 4,000 males has fragile X syndrome.• Between 1 in 100 and 1 in 500 females are estimated to carry the premutation for fragile X syndrome and be variably affected.• Between 1 in 5,000 and 1 in 8,000 females have fragile X syndrome.Investigations• Fragile X DNA testing should be considered for all people with an unknown cause of developmental delay. DNA studies offer a definitive result for affected individuals and carriers.• The DNA test is available on the MBS, and requests must specify fragile X syndrome. The MBS criteria for testing are: > A patient with one or more of the clinical features of fragile X syndrome > A patient who has a relative with a fragile X mutation• Testing should always be performed with appropriate pre- and post-genetic test counselling.Preconception testing• DNA studies to determine carrier status for those with a family history of fragile X syndrome.Prenatal testing• DNA studies can be offered using specimens obtained via chorionic villus sampling or amniocentesis.• A positive result for fragile X syndrome does not indicate the degree of intellectual disability, which varies greatly between individuals.• Depending on test results, termination of pregnancy may be considered by the parents. • Referral for specialist genetic counselling is recommended (see Contacts, support and testing)

Management• While there is no cure for fragile X syndrome, a wide range of specific treatment and management strategies are available, which involve multiple health professionals as well as the parents and carers, and are of great benefit to affected individuals and their families. These include: > Genetic counselling > Grief and anger counselling

> Support for families, including the assistance of a community worker or social worker > Early intervention, ongoing speech and occupational therapies > Management of behavioural issues (sensory defensiveness, hyperarousal and attention problems) — Some clinicians find that behavioural symptoms may respond well to SSRIs (selective serotonin re-uptake inhibitors) and psychostimulants > Educational strategies > Maximising strengths > Pharmacological management of medical issues including epilepsy, attention disorders, aggression and mood disorders

Implications for other family members• If an individual tests positive for a fragile X full mutation or premutation, their family should be referred to Genetics Services for counselling.• The individual and their family should be supported in discussing fragile X syndrome with their extended family, as counselling and genetic testing should be offered to those relatives at risk of having the fragile X mutation. • Detection of fragile X carriers allows families to make informed decisions regarding family planningReferral Information• Refer to paediatric and Genetics Services for assessment. Genetics Services will provide information regarding availability of multidisciplinary clinics for fragile X syndrome (see Contacts, support and testing).• Refer to your local AGA Peak Body (see Contacts, support and testing) to find a relevant support group.

Autism• Autism is characterised by impairment in verbal and nonverbal communication, imaginative play activity and social interaction.• Between 3 in 1,000 and 4 in 10,000 individuals have autism.• Onset is prior to 30 months of age.• Around 80% have learning disability. • Categorised within pervasive developmental conditions which also includes Asperger syndrome, childhood disintegrative disorder and Rett syndrome.• May co-exist with other conditions including: intellectual disability, speech and language conditions, anxiety and depression, epilepsy, attention disorders, Tourette syndrome and Down syndrome. • It is important to exclude specific genetic developmental conditions, specifically minor chromosomal changes and fragile X syndrome, and autistic-like features of ID.• Autistic features can be the presenting symptoms in ID and other genetic conditions.

• Early diagnosis and intervention for a child with autism has been shown to improve outcomes and maximise learning opportunities. While there is no cure, a wide range of specific treatments and management strategies are available. Early diagnosis also ensures families and carers have better access to services and professional support.• There is no clear inheritance pattern, however family and twin studies have shown there is a familial component to autism and pervasive developmental delay conditions.• As yet there is no known single gene that causes autism and therefore genetic testing is not available. Underlying genetic conditions in children presenting with autistic features • Tuberous sclerosis, characterised by epilepsy, DD, depigmented macules • Fragile X syndrome • Chromosomal abnormalities, eg inversions, duplications, 15q deletions • Metabolic conditions • Rett syndrome, characterised by language and motor regression, loss of purposeful movement

At-risk individuals• Individuals, especially males with: > A close family history of autism or related pervasive developmental delay disorder > Autistic-like features• Tests that may be relevant for individuals with autistic features include: > Karyotype > Fragile X DNA testing > Repeat tests for newborn screening• Refer to: > Paediatrician for assessment of autistic features > Genetics Services if the individual is dysmorphic > Neurologist if regression of psychomotor skills occurs > AGA Peak Body for an appropriate support group (see Contacts, support and testing)• It is estimated that there is a 5% recurrence risk for siblings of children affected with autism.

Patient and family fact sheetDevelopmental delay and intellectual disability

Developmental delay and intellectual disability are similar phrases. They describe aspects of a person who is either slow to develop, or has not fully developed, in some of the following areas: speech, language, mental capacity or physical capacity.

Developmental delay and intellectual disability can be extremely mild or they can be quite severe. Some people with developmental delay or intellectual disability lead normal lives, while others have very restricted lives and need care outside the family.Sometimes children with developmental delay and intellectual disability are picked up soon after birth. Sometimes the problems are noticed when children are slow to learn to talk. Sometimes

problems are not detected until the child starts school. Quite often, the parents have suspected there is a problem well before it is diagnosed by doctors.There are many different causes of developmental delay and intellectual disability. Some of the causes include infections, injuries, difficult births and autism. Genetic conditions can also cause developmental delay or intellectual disability. The most common ones are: • Chromosomal conditions, such as Down syndrome • Single gene conditions, such as fragile X syndrome (which causes intellectual disability and a range of behavioural problems) or phenylketonuria (where the body lacks a specific enzyme, which causes abnormal metabolism that may result in brain damage).

In some cases, when someone in the family has developmental delay or intellectual disability, it is wise to discuss whether or not other family members need to be assessed. It is also wise to see whether or not any genetic testing is available.While there is no cure for any form of developmental delay or intellectual disability, finding out the cause early and getting help from a wide range of professionals, can help. Some young children with developmental delay can catch up.

Daftar Pustaka

Yuwono, Tribuwono. 2005. Biologi Molekuler. Jakarta: Erlangga.www.oadd.org/Journal diakses tanggal 14 Oktober 2014depts..washinton.edu/geneticcounseling diakses tanggal 14 Oktober 2014