Sadika A. Al-Awadi

Consanguinity among the Kuwaiti population

A total of 5,007 Kuwaitis were ascertained to study the incidence of consanguineous marriages during 1983. The rate of consanguineous mating was found to be 54.3% with estimated population incidence rates 52.9 to 55.7%. First cousin marriages were the most frequent type. The average inbreeding coefficient was 0.0219 which could be considered high.

Profound limb deficiency, thoracic dystrophy, unusual facies, and normal intelligence: a new syndrome.

A newly recognised profound limb deficiency malformation syndrome in two Arab sibs of different sexes with consanguineous parents is described. Additional features, which include thoracic dystrophy, unusual facies, and normal intelligence, are consistent in both of them. Autosomal recessive inheritance is suggested.

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.

Deletion analysis of the SMN and NAIP genes in Kuwaiti patients with spinal muscular atrophy

Two genes are known to be involved in spinal muscular atrophy (SMA), namely, SMN (survival motor neuron) and NAIP (neuronal apoptosis inhibitory protein). Deletion analysis of these genes has been reported for many ethnic groups. We have extended this analysis to include 15 Arabic patients (11 unrelated cases of type I, which represent practically all of the patients diagnosed within the last 2 years in Kuwait, and 4 type-II cases from a single kinship). Also, 41 healthy relatives (parents and sibs) and 44 control individuals of Arabic origin were analyzed. The homozygous deletions of exons 7 and 8 of the SMN gene were found in all SMA patients studied. Exon 5 of NAIP was homozygously absent in all type-I patients, but was retained in type-II cases. Among members of SMA families, one mother was found to be homozygously deleted for NAIP. All of the control individuals had both normal SMN and NAIP. Our results are in agreement with the general consensus that the incidence of NAIP deletion is higher in the more severe SMA cases. Furthermore, they suggest that SMA type-I chromosomes, with the dual deletion of the SMN and NAIP genes, are more common in Arabs than in patients of other ethnic origin.

Profile of Chromosomal Abnormalities in the Al Jahra Region of Kuwait

Objective: One hundred and seventy-seven newborn babies with chromosomal abnormalities were studied at the Al-Jahra satellite clinic of the Kuwait Medical Genetics Centre (KMGC), Kuwait, over a 7-year period from January 1983 to December 1989 to make a reanalysis and recomputation of the statistical results of the previous short-term studies. Methods: The data were collected from the registry of chromosomal abnormalities and from the clinical records of the patients in KMGC retrospectively. Controls were selected from the newborn babies delivered in the same period of study. The logistic regression analysis was computed using dependent/independent variables. Results: Ninety-five percent of the cases had numerical chromosomal abnormalities, and 5% had structural chromosomal abnormalities. One hundred and forty-five cases had classic trisomy 21, with an incidence of 2.9/1,000 live births (LB), 16 cases had trisomy 18 (0.3/1,000 LB), 5 cases had trisomy 13 (0.1/1,000 LB), 1 case had triploidy 69, XXY (0.02/1,000 LB) and 1 had Turner’s syndrome (0.05/1,000 female LB). Nine cases with structural chromosomal abnormalities were enumerated, dir dup(1) (p21–p32), del(1)(q32–q42), del(13)(q22–q34) and inversion Y chromosome, the incidence was 0.02/1,000 LB for each. Two cases of translocation trisomy 21 (0.04/1,000 LB) and 3 cases of cri-du-chat (0.06/1,000 LB) were enumerated too. Bedouins had a double-fold increased risk of trisomy 21 (odds ratio = 1.819, p = 0.032), and advanced maternal age was also a risk factor while paternal age showed inconsistent pattern of risk. Conclusion: This study confirmed the high incidence of the common trisomies and the role of advanced maternal age and the Bedouin ethnicity as a risk factor.

Population Study of Common Glucose-6-Phosphate Dehydrogenase Mutations in Kuwait

DNA samples from 206 unrelated Kuwaitis of both sexes, i.e. 200 randomly selected individuals and 6 glucose-6-phosphate-dehydrogenase (G6PD)-deficient probands, have been analyzed by the PCR/RFLP technique for mutations underlying the most common G6PD-deficient variants (Mediterranean and A–). At the first step all samples were studied for the 563C→T and 376A→G mutations, then the samples positive for 376A→G were further analyzed for 202G→A, 680G→T and 968T→C mutations. Three mutations (563C→T, 376A→G and 202G→A) were found to be present in the Kuwaiti population at polymorphic frequencies (0.0503, 0.0215 and 0.0111, respectively). Nineteen out of 20 unrelated Kuwaiti chromosomes with 563C→T had Mediterranean haplotype as judged by 1311C→T polymorphism. The frequency of G6PD-deficient genotypes was 4.5% (5.73% in males and 2.56% in females).

Osteoporosis-pseudoglioma syndrome with congenital heart disease: a new association

We report a sibship of two brothers and one sister with the osteoporosis-pseudoglioma syndrome and congenital heart disease. They presented in infancy with visual impairment and psychomotor retardation. Major features included bilateral cataracts, generalised osteopenia, severe platyspondyly, borderline mental retardation, muscular hypotonia, joint laxity, and ventricular septal defect. Parental consanguinity and affected sibs of both sexes strongly suggested autosomal recessive inheritance. Analysis of the present and previously reported cases showed a wide range of interfamilial variability which may point to the existence of multiple allelism or genetic heterogeneity in this syndrome.

Disease profile of 400 institutionalized mentally retarded patients in Kuwait

Farag TI, Al‐Awadi SA, El‐Badramary MH, Aref MA, Kasrawi B, Krishna Murthy DS, El‐Khalifa MY, Yadav G, Marafie MJ, Bastaki L, Wahba RA, Mohammed FM, Abul Hasan S, Redha AA, Redha MA, Al‐aboud H, Al‐Hijji S, Al‐Dighashem D, Al‐Hashash N, Al‐Jeeryan L, Al‐Khor‐afi H, Qurban EA, Al‐Sulaiman I. Disease profile of 400 institutionalized mentally retarded patients in Kuwait.

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.