A Novel Mutation in the Transglutaminase-1 Gene in an Autosomal Recessive Congenital Ichthyosis Patient

Structure-function implication on a novel homozygous Trp250/Gly mutation of transglutaminase-1 (TGM1) observed in a patient of autosomal recessive congenital ichthyosis is invoked from a bioinformatics analysis. Structural consequences of this mutation are hypothesized in comparison to homologous enzyme human factor XIIIA accepted as valid in similar structural analysis and are projected as guidelines for future studies at an experimental level on TGM1 thus mutated.

The descriptive epidemiology of congenital and acquired cryptorchidism in a UK infant cohort.

INTRODUCTION: Recent studies in other European countries suggest that the prevalence of congenital cryptorchidism continues to increase. This study aimed to explore the prevalence and natural history of congenital cryptorchidism in a UK centre. METHODS: Between October 2001 and July 2008, 784 male infants were born in the prospective Cambridge Baby Growth Study. 742 infants were examined by trained research nurses at birth; testicular position was assessed using standard techniques. Follow-up assessments were completed at ages 3, 12, 18 and 24 months in 615, 462, 393 and 326 infants, respectively. RESULTS: The prevalence of cryptorchidism at birth was 5.9% (95% CI 4.4% to 7.9%). Congenital cryptorchidism was associated with earlier gestational age (p<0.001), lower birth weight (p<0.001), birth length (p<0.001) and shorter penile length at birth (p<0.0001) compared with other infants, but normal size after age 3 months. The prevalence of cryptorchidism declined to 2.4% at 3 months, but unexpectedly rose again to 6.7% at 12 months as a result of new cases. The cumulative incidence of "acquired cryptorchidism" by age 24 months was 7.0% and these cases had shorter penile length during infancy than other infants (p = 0.003). CONCLUSIONS: The prevalence of congenital cryptorchidism was higher than earlier estimates in UK populations. Furthermore, this study for the first time describes acquired cryptorchidism or "ascending testis" as a common entity in male infants, which is possibly associated with reduced early postnatal androgen activity.

A short in-frame deletion in NTRK1 tyrosine kinase domain caused by a novel splice site mutation in a patient with congenital insensitivity to pain with anhidrosis

Background: Congenital insensitivity to pain with anhidrosis (CIPA) is a rare autosomal recessive genetic disease characterized by the lack of reaction to noxious stimuli and anhidrosis. It is caused by mutations in the NTRK1 gene, which encodes the high affinity tyrosine kinase receptor I for Neurotrophic Growth Factor (NGF). -- Case Presentation: We present the case of a female patient diagnosed with CIPA at the age of 8 months. The patient is currently 6 years old and her psychomotor development conforms to her age (RMN, SPECT and psychological study are in the range of normality). PCR amplification of DNA, followed by direct sequencing, was used to investigate the presence of NTRK1 gene mutations. Reverse transcriptase (RT)-PCR amplification of RNA, followed by cloning and sequencing of isolated RT-PCR products was used to characterize the effect of the mutations on NTRK1 mRNA splicing. The clinical diagnosis of CIPA was confirmed by the detection of two splice-site mutations in NTRK1, revealing that the patient was a compound heterozygote at this gene. One of these alterations, c.574+1G > A, is located at the splice donor site of intron 5. We also found a second mutation, c.2206-2 A > G, not previously reported in the literature, which is located at the splice acceptor site of intron 16. Each parent was confirmed to be a carrier for one of the mutations by DNA sequencing analysis. It has been proposed that the c.574+1G > A mutation would cause exon 5 skipping during NTRK1 mRNA splicing. We could confirm this prediction and, more importantly, we provide evidence that the novel c.2206-2A > G mutation also disrupts normal NTRK1 splicing, leading to the use of an alternative splice acceptor site within exon 17. As a consequence, this mutation would result in the production of a mutant NTRK1 protein with a seven aminoacid in-frame deletion in its tyrosine kinase domain. --Conclusions: We present the first description of a CIPA-associated NTRK1 mutation causing a short interstitial deletion in the tyrosine kinase domain of the receptor. The possible phenotypical implications of this mutation are discussed.

Exclusive gene mapping of congenital microphthalmia in a Chinese family

Congenital microphthalmia is a developmental ocular disorder and might be caused by the mutations in the genes involved in eye development. To uncover the genetic cause in a six-generation Chinese pedigree with autosomal dominant congenital microphthalmia

Localization of a novel gene for congenital nonsyndromic simple microphthalmia to chromosome 2q11-14

Microphthalmia is a clinically and genetically heterogeneous disorder of eye development. The genetic basis of nonsyndromic microphthalmia is not yet fully understood. Previous studies indicated that disease pedigrees from different genetic backgrounds co

Mutation analysis of a large Chinese pedigree with congenital preaxial polydactyly

Mutations in the long-range limb-specific cis-regulator (ZRS) could cause ectopic shh gene expression and are responsible for preaxial polydactyly (PPD). In this study, we analyzed a large Chinese isolated autosomal dominant PPD pedigree. By fine mapping

Safety of tetanus toxoid in pregnant women: A hospital-based case-control study of congenital anomalies

Reported are the results of the Latin American Collaborative Study of Congenital Malformations (ECLAMC), a hospital-based case-control study of 34 293 malformed and 34 477 matched nonmalformed newborn controls. No statistical differences were found between the malformed and control groups, exposed or not exposed to tetanus toroid.

CRYBB1 mutation associated with congenital cataract and microcornea

The molecular characterization of a UK family with an autosomal dominant congenital cataract associated with microcornea is reported. METHODS: Family history and clinical data were recorded. This phenotype was linked to a 7.6 cM region of chromosome 22q11.2-q12.2, spanning the beta-crystallin gene cluster (ZMax of 3.91 for marker D22S1114 at theta=0). Candidate genes were PCR amplified and screened for mutations on both strands using direct sequencing. RESULTS: Sequencing of the coding regions and flanking intronic sequences of CRYBB2 and CRYBB1 showed the presence of a novel, heterozygous X253R change in exon 6 of CRYBB1. SSCP analysis confirmed that this sequence change segregated with the disease phenotype in all available family members and was not found in 109 ethnically matched controls. CONCLUSIONS: X253R is predicted to elongate the COOH-terminal extension of the protein and would be expected to disrupt beta-crystallin interactions. This is the first documented involvement of CRYBB1 in ocular development beyond cataractogenesis.