Kamal K. Naguib

Complex translocation involving chromosomes Y, 1, and 3 resulting in deletion of segment 3q23----q25.

describe what is, to our knowledge, the first familial case of pericentric inversion of chromosome 1 involving the whole of the short arm and associated with infertility. The proband was a male aged 35 who came to our laboratory because of sterility. He reported a 33 year old brother who had been married for two years without children. Both patients had normal phenotypes and no history of testicular pathology. Semen analysis showed severe oligozoospermia in both and the few spermatozoa present were immotile. The patients refused testicular biopsy. Chromosome preparations in the proband and his brother, obtained from peripheral blood lymphocytes, were examined after G, C, and high resolution R banding. G and R banding revealed in both an inverted short arm of chromosome 1 with the centromere located near the terminal part of the chromosome. C banding showed two blocks of C heterochromatin, the smaller one located in a subterminal position. This suggested that the breakpoints were at 1p36-3 and 1q12 (fig 1). This unusual pericentric inversion was also found in the mother of the proband, inv(1)(p36.3ql2), showing that the inverted chromosome was inherited without meiotic recombination in the inverted segment. The karyotype of 11.5 was normal (fig 2). In this case, as in the three others previously reported, it is reasonable to assume that there may be an association between the inversion and failure of spermatogenesis.

Spondyloepiphyseal dysplasia tarda with progressive arthropathy.

We present a family with numerous first cousin marriages and several members affected with spondyloepiphyseal dysplasia tarda with progressive arthropathy causing severe crippling and deformity. The extensive pedigree provides strong evidence for autosomal recessive inheritance.

New autosomal recessive faciodigitogenital syndrome.

Most pedigrees of Aarskogs faciodigitogenital syndrome have suggested X linked inheritance. However, sex influenced autosomal dominant inheritance is also a possibility in some families. We describe an Arab family of normal consanguineous parents with five children (three males and two females) with some features of Aarskog syndrome in addition to some unusual hair changes. The possibility that this family represents a distinct previously unrecognised faciodigitogenital syndrome with short stature and hair abnormalities is suggested and discussed.

Fertility with deletion Xq25: report of three cases; possible exceptions for critical region hypothesis

We report on an Arab family in which a mother and two of her daughters, despite having deletion Xq25, are fertile. So far, only one case of deletion Xq25 associated with fertility has been reported. Consistent inactivation of the deleted X chromosome in the proposita and early menopause in the mother were noted. The effect of Xq deletion on fertility and the CRH is discussed.

Human homologue for the mouse mutant disorganisation: does it exist?

We describe a newborn Arab male with defects similar to those seen in mice heterozygous for the mutant disorganisation (DS) gene. He had complete absence of the left lower limb including the left pelvic bone, hamartomas arising from the abdominal wall, a small penis, absent left half of the scrotal sac, absent left testicle, anterior displacement of the anus, and multiple vertebral defects. The similarity between the probands anomalies and those found in affected heterozygotes for DS support the possibility of a human homologue of the DS gene.

Persistent Mullerian duct syndrome: Report of two boys with associated crossed testicular ectopia

Persistent Mullerian duct structures and crossed testicular ectopia were found in two phenotypically normal, unrelated males, with 46,XY karyotype, during routine herniorrhaphy. In each case, the vascular supply to the ectopic testis originated from the appropriate ipsilateral side. The clinical significance and genetic implications of this rare association are discussed.

Brachmann-de Lange syndrome in sibs.

We report an Arab family of phenotypically normal first cousin parents with two offspring showing variable manifestations of Brachmann-de Lange syndrome. The proband, who had many diagnostic symptoms of the syndrome with apparently normal chromosomes, died at the age of three months. His sister was less severely affected and lived for six years. The genetic basis of Brachmann-de Lange syndrome is discussed and homozygosity for an autosomal recessive allelle is suggested as an underlying cause in some cases.

Hypoplastic tibiae with postaxial polysyndactyly: a new dominant syndrome?

A five year old boy is reported with hypoplastic, bowed tibiae and postaxial polysyndactyly. Sixteen relatives of both sexes in four generations either have bilateral syndactyly or postaxial polydactyly or both. The nature of the condition and the possible mode of inheritance are discussed.

Clustering of trisomy 18 in Kuwait: Genetic predisposition or environmental?

BACKGROUND This study describes 59 newborns with regular trisomy 18 (EdwardsA centAA syndrome, T18) who were ascertained clinically and cytogenetically at the Kuwait Medical Genetic Centre from 1994 to 1997, out of 118 T18 cases identified from 1980 to 1997. MATERIALS AND METHODS T18 cases were ascertained clinically and cytogenetically shortly after birth. In addition to assessing the T18 birth prevalence rate and confidence limits during the years 1994-1997, we investigated the possible etiological factors by a case-control study with normal healthy newborns. Studied factors included gender, parental age, birth order, abortion, clinical variables (presentation, amniotic fluid and mode of delivery), and survival. RESULTS The average T18 birth prevalence rate during the period was 8.95 per 10,000 live births (95% confidence limits 6.66-11.23). The T18 cases were mostly females, with a male:female ratio of 1:2.1, and the majority (53%) died before the second week of life. Maternal age above 30 years was found to be a significant factor for T18. CONCLUSION This high T18 birth prevalence rate suggests clustering of T18 in the highly inbred population of Kuwait. Such clustering may indicate a possible environmental, and to a lesser extent, genetic predisposition to aneuploidy nondisjunction.

Connexin 26 Gene Mutations in Non-Syndromic Hearing Loss Among Kuwaiti Patients

Objective: To study connexin 26 (Cx26) gene mutations among autosomal recessive non-syndromal hearing loss in Kuwaiti patients and evaluate their effect on phenotypes. Subjects and Methods: This cross sectional study included 100 patients aged between 6 months and 18 years, who were referred to the Sheikh Salem Al-Ali Centre for audiology and speech evaluation of autosomal recessive non-syndromic sensorineural hearing loss confirmed by clinico-genetic evaluation and a battery of diagnostic tests. Gene profiling and sequencing were performed to detect the presence and nature of Cx26 mutation. Results: Of the 100 patients, mutation of Cx26 gene was detected in 15 patients (15%) of which 9 (60%) cases were heterozygous and 6 cases (40%) were homozygous. Eighty per cent of the 15 Cx26 positive cases resulted from the 35delG mutation. Among the heterozygous cases, 6 (66.6%) were positive for 35delG. All 6 homozygous patients were positive for the 35delG mutation. A significant correlation was found between genetic findings (p = 0.013) and family history (p = 0.029), as well as the onset (p = 0.015), course (p = 0.033), degree and configuration of hearing loss (p = 0.001). Conclusion: Among the selected Kuwaiti population sample, the Cx26 gene mutation was responsible for 15% of autosomal recessive non-syndromic sensorineural hearing loss. We recommend that screening for Cx26 gene mutation be considered in the screening strategy of patients with non-syndromic childhood hearing loss for counselling and management purposes.