GM25952
Fibroblast from Skin, Skin
Description:
MENTAL RETARDATION, X-LINKED 102; MRX102
DEAD/H BOX 3, X-LINKED; DDX3X
|
Repository
|
NIGMS Human Genetic Cell Repository
|
| Subcollection |
Heritable Diseases
PIGI Consented Sample |
|
Biopsy Source
|
Skin
|
|
Cell Type
|
Fibroblast
|
|
Tissue Type
|
Skin
|
|
Transformant
|
Untransformed
|
|
Sample Source
|
Fibroblast from Skin, Skin
|
|
Race
|
White
|
|
Ethnicity
|
Not Hispanic/Latino
|
|
Country of Origin
|
USA
|
|
Family Member
|
1
|
|
Family History
|
N
|
|
Relation to Proband
|
proband
|
|
Species
|
Homo sapiens
|
|
Common Name
|
Human
|
|
Remarks
|
|
| PDL at Freeze |
6.9 |
| Passage Frozen |
3 |
| |
| IDENTIFICATION OF SPECIES OF ORIGIN |
Species of Origin Confirmed by LINE assay |
| |
| Gene |
DDX3X |
| Chromosomal Location |
Xp11.4 |
| Allelic Variant 1 |
p.Q417P; Mental retardation, X-linked 102 |
| Identified Mutation |
c.1250 A>C; In 3 unrelated girls with X-linked mental retardation-102 (MRX102; 300958), Snijders Blok et al. (2015) identified a de novo heterozygous c.1126C-T transition (c.1126C-T, NM_001356.4) in the DDX3X gene, resulting in an arg376-to-cys (R376C) substitution in the helicase ATP-binding domain. The mutations were found by whole-exome sequencing of several large cohorts of patients with intellectual disability; R376C was not found in the ExAC or Exome Variant Server databases. In vitro cellular functional expression studies and in vivo studies in zebrafish indicated that the R376C mutation caused a loss of protein function, consistent with haploinsufficiency |
| Remarks |
Clinically affected; symptom onset at 6 months; diagnosed at age 9 years; breech presentation, labor induced at 37.5 weeks; birth measurements: weight 3.04 kg, length 51 cm, occipitofrontal circumference 34.5 cm; admitted 4 days for spontaneous pneumothorax; extreme irritability noted in first six months of life; recurrent middle ear effusion-otitis (12 ear infections reported between ages 2 and 3); hypotonia; rolled at 6 months; sat up at 12 months; crawled at 12 months; stood/cruised at 14 months; walked alone at 18 months; global developmental delay; delayed receptive and expressive language; moderate intellectual disability; first words 18 months; 3-4 word sentences by 34 months; by age 36 months naming colors 60% correct, animal sounds, and counting; estimated mental age/DQ of 0.6 (functioning at the level of a 5-6 year old at age 9); can perform some complex tasks and has islands of comprehension and expressive language; strong social attachments, reciprocal and some imaginative play; normal pointing; good adaptive function; attention deficit disorder; brain MRI detected prominence of temporal horns L>R; whole exome sequencing revealed subject is heterozygous for de novo Q417P (CAG>CCG): c.1250 A>C variant in exon 12 of the DDX3X gene; karyotype and Signature Genomics 3.0 BAC array were normal; surgery: myringotomy tubes; medications/supplements: Methylphenidate Hydrochloride (Concerta), Levothyroxine Sodium (Levo-T), probiotic; subject’s parents and three siblings do not harbor the Q417P variant in the DDX3X gene; unaffected mother is GM25953; subject is "Individual 30" in the publication by Snijders Blok, et al (PMID 26235985). |
| Snijders Blok L, Madsen E, Juusola J, Gilissen C, Baralle D, Reijnders MR, Venselaar H, Helsmoortel C, Cho MT, Hoischen A, Vissers LE, Koemans TS, Wissink-Lindhout W, Eichler EE, Romano C, Van Esch H, Stumpel C, Vreeburg M, Smeets E, Oberndorff K, van Bon BW, Shaw M, Gecz J, Haan E, Bienek M, Jensen C, Loeys BL, Van Dijck A, Innes AM, Racher H, Vermeer S, Di Donato N, Rump A, Tatton-Brown K, Parker MJ, Henderson A, Lynch SA, Fryer A, Ross A, Vasudevan P, Kini U, Newbury-Ecob R, Chandler K, Male A, DDD Study A, Dijkstra S, Schieving J, Giltay J, van Gassen KL, Schuurs-Hoeijmakers J, Tan PL, Pediaditakis I, Haas SA, Retterer K, Reed P, Monaghan KG, Haverfield E, Natowicz M, Myers A, Kruer MC, Stein Q, Strauss KA, Brigatti KW, Keating K, Burton BK, Kim KH, Charrow J, Norman J, Foster-Barber A, Kline AD, Kimball A, Zackai E, Harr M, Fox J, McLaughlin J, Lindstrom K, Haude KM, van Roozendaal K, Brunner H, Chung WK, Kooy RF, Pfundt R, Kalscheuer V, Mehta SG, Katsanis N, Kleefstra T, Mutations in DDX3X Are a Common Cause of Unexplained Intellectual Disability with Gender-Specific Effects on Wnt Signaling American journal of human genetics97:343-52 2015 |
| PubMed ID: 26235985 |
| Cumulative PDL at Freeze |
6.9 |
| Passage Frozen |
3 |
| Split Ratio |
1:6 |
| Temperature |
37 C |
| Percent CO2 |
5% |
| Percent O2 |
3% |
| Medium |
Eagles Minimum Essential Medium with Earle's salts:Dulbecco's modified MEM with 2mM L-glutamine or equivalent |
| Serum |
15% fetal bovine serum Not inactivated |
| Substrate |
None specified |
| Supplement |
- |
|