A 3-base pair deletion, c.9711_9713del, in DMD results in intellectual disability without muscular dystrophy.

We have identified a deletion of 3 base pairs in the dystrophin gene (DMD), c.9711_9713del, in a family with nonspecific X-linked intellectual disability (ID) by sequencing of the exons of 86 known X-linked ID genes. This in-frame deletion results in the deletion of a single-amino-acid residue, Leu3238, in the brain-specific isoform Dp71 of dystrophin.

Recurrent deletion of ZNF630 at Xp11.23 is not associated with mental retardation.

ZNF630 is a member of the primate-specific Xp11 zinc finger gene cluster that consists of six closely related genes, of which ZNF41, ZNF81, and ZNF674 have been shown to be involved in mental retardation. This suggests that mutations of ZNF630 might influence cognitive function. Here, we detected 12 ZNF630 deletions in a total of 1,562 male patients with mental retardation from Brazil, USA, Australia, and Europe.

Xq13.2q21.1 duplication encompassing the ATRX gene in a man with mental retardation, minor facial and genital anomalies, short stature and broad thorax.

In a man with severe mental retardation, minor facial and genital anomalies, disproportionate short stature and a broad thorax, we identified a de novo Xq13.2q21.1 duplication by array CGH.

Structural variation in Xq28: MECP2 duplications in 1% of patients with unexplained XLMR and in 2% of male patients with severe encephalopathy.

Duplications in Xq28 involving MECP2 have been described in patients with severe mental retardation, infantile hypotonia, progressive spasticity, and recurrent infections. However, it is not yet clear to what extent these and accompanying symptoms may vary. In addition, the frequency of Xq28 duplications including MECP2 has yet to be determined in patients with unexplained X-linked mental retardation and (fe)males with severe encephalopathy.

Homozygous mutation in SPATA16 is associated with male infertility in human globozoospermia.

Globozoospermia is a rare (incidence <0.1% in male infertile patients) form of teratozoospermia, mainly characterized by round-headed spermatozoa that lack an acrosome. It originates from a disturbed spermiogenesis, which is expected to be induced by a genetic factor.

Mutation frequencies of X-linked mental retardation genes in families from the EuroMRX consortium.

The EuroMRX family cohort consists of about 400 families with non-syndromic and 200 families with syndromic X-linked mental retardation (XLMR). After exclusion of Fragile X (Fra X) syndrome, probands from these families were tested for mutations in the coding sequence of 90 known and candidate XLMR genes. In total, 73 causative mutations were identified in 21 genes.

Loss-of-function mutations in euchromatin histone methyl transferase 1 (EHMT1) cause the 9q34 subtelomeric deletion syndrome.

A clinically recognizable 9q subtelomeric deletion syndrome has recently been established. Common features seen in these patients are severe mental retardation, hypotonia, brachycephaly, flat face with hypertelorism, synophrys, anteverted nares, cupid bow or tented upper lip, everted lower lip, prognathism, macroglossia, conotruncal heart defects, and behavioral problems. The minimal critical region responsible for this 9q subtelomeric deletion (9q-) syndrome has been estimated to be <1 Mb and comprises the euchromatin histone methyl transferase 1 gene (EHMT1).

ZNF674: a new kruppel-associated box-containing zinc-finger gene involved in nonsyndromic X-linked mental retardation.

Array-based comparative genomic hybridization has proven to be successful in the identification of genetic defects in disorders involving mental retardation. Here, we studied a patient with learning disabilities, retinal dystrophy, and short stature. The family history was suggestive of an X-linked contiguous gene syndrome.

Expanding phenotype of XNP mutations: mild to moderate mental retardation.

Mutations in the XNP gene have been reported in alpha thalassemia/mental retardation (MR) syndrome (ATR-X) and other severe X-linked MR conditions with facial dysmorphisms. In this report, we describe a missense mutation in exon 18 in a family with borderline to moderate MR. Like other disorders associated with an XNP mutation, skewed X-inactivation was found in all carrier females in this family.

Low frequency of MECP2 mutations in mentally retarded males.

A high frequency of mutations in the methyl CpG-binding protein 2 (MECP2) gene has recently been reported in males with nonspecific X-linked mental retardation. The results of this previous study suggested that the frequency of MECP2 mutations in the mentally retarded population was comparable to that of CGG expansions in FMR1. In view of these data, we performed MECP2 mutation analysis in a cohort of 475 mentally retarded males who were negative for FMR1 CGG repeat expansion.

Familial oligoasthenoteratozoospermia: evidence of autosomal dominant inheritance with sex-limited expression.

Objective: To report the familial occurrence of severe oligoasthenoteratozoospermia in a man and five male relatives related through their mothers.

Design: Case report.

Setting: University medical center.