J. M. Cantú

A distinct osteochondrodysplasia with hypertrichosis—Individualization of a probable autosomal recessive entity

SummaryTwo sibs and two other unrelated patients presented a distinct previously undescribed syndrome consisting of generalized congenital hypertrichosis, macrosomy at birth, narrow thorax, cardiomegaly, wide ribs, platyspondyly, hypoplastic ischiopubic branches, small obturator foramen, bilateral coxa valga, enlarged medullar canal, long bones shaped like an ‘Erlenmeyer flasks’ and generalized osteopenia. The family data suggest autosomal recessive inheritance.

The C677T polymorphism of the methylenetetrahydrofolate reductase gene in Mexican mestizo neural-tube defect parents, control mestizo and native populations.

The C677T mutation of the methylenetetrahydrofolate reductase (MTHFR) gene, associated with the thermolabile form of the enzyme, has reportedly been found to be increased in neural-tube defects (NTD), though this association is still unclear. A group of 107 mestizo parents of NTD children and five control populations: 101 mestizo (M), 50 Huichol (H), 38 Tarahumara (T), 21 Purepecha (P) and 20 Caucasian (C) individuals were typed for the MTHFR C677T variant by the PCR/RFLP (HinfI) method. Genotype frequencies were in agreement with the Hardy-Weinberg expectations in all six populations. Allele frequency (%) of the C677T variant was 45 in NTD, 44 in M, 56 in H, 36 in T, 57 in P, 35 in C. Pairwise inter-population comparisons of allele frequency disclosed a very similar distribution between NTD and M groups (exact test, P=0.92). Among controls, differences between M and individual native groups were NS (0.06<P<0.21), as it was between M and C (P=0.29). A high frequency of the variant was found in H (56%) and P (57%). A similar allele frequency in groups M and NTD does not support a causal relationship between NTD and parental MTHFR C677T genotypes. Thus, the C677T variant cannot be regarded as a major genetic risk factor for NTD in Mexican mestizo parents. Otherwise, C677T in Mexico is very frequent, especially in Huichol and Purepecha natives, as compared with other groups world wide.

A distinct variant of the Ehlers-Danlos syndrome

Two unrelated males presented a distinct syndrome, consisting mainly of mental retardation, short stature, wrinkled facies, curly and fine hair, scanty eyebrows and eyelashes, telecanthus, periodontitis, hypermobility of the joints, hyperextensibility and fragility of the skin, multiple nevi, papiraceous scars, bruisability, varicose veins, pectus excavatum, winged scapulae, pes planus and bilateral cryptorchidism. Since some features were typical of Ehlers‐Danlos Syndrome (EDS), the clinical data were analyzed comparatively with the different types of EDS. The individualization of a distinct variant is concluded. Increased paternal age at the birth of both cases suggests a de novo dominant mutation.

Centric fission, centromere‐telomere fusion and isochromosome formation: a possible origin of a de novo 12p trisomy

A 5‐month‐old girl had a typical 12p trisomy syndrome due to a monocentric i(12p) present in a 46‐chromosome complement that also included the translocation of all 12q onto the 8p telomere; i.e., her complex karyotype could be written as 46.XX, – 8,–12,+ der(8),t(8;12)(p23.3;cen), + i(12p). The present concurrence of a whole‐arm q translocation and an i(p) for a single chromocome, along with six previous similar instances involving chromosomes 4, 5 and 9, suggests the following origin for such a special rearrangement: a centric fission in Gl initially yielding two telocentrics; at the next replication, the tel(q) translocates onto a nonhomologous telomere (centromere‐telomere fusion), whereas the tel(p) becomes an i(p). This mechanism can be either meiotic or postzygotic and surmises that the translocated long arm retains a partial centromere, which subsequently is inactivated and loses its staining properties.

Pure monosomy and trisomy 2q24.2→q3105 due to an inv ins(7;2)(q21.2;q3105q24.2) segregating in four generations

SummaryAn inv ins(7;2)(q21.2;q3105q24.2) was found to segregate through four generations of a family. Adjacent-1 segregation aneusomies were ascertained in five patients: three monosomics and two trisomics; and the corresponding syndromes were delineated. The comparative analysis between these and other previously described 2q aneusomic individuals led to the conclusion that a large cleft between first and second toes is a constant feature in monosomy 2q24→q31. No other trait could plausible be mapped. Risks of 7.9 to 31.9% for aneusomic children and of 26.3% for abortion were estimated in the present family.

Autosomal recessive microcephaly associated with chorioretinopathy

SummaryTwo sisters and their brother affected with microcephaly, microphthalmia, chorioretinal degeneration, and optic atrophy were studied. Besides the clinical features derived from the main abnormalities, nanosomy and cutis marmorata were found in the three patients. Both parents and three other sibs were normal. Possible intrauterine non-genetic etiologic factors (X-rays, toxoplasmosis, cytomegalovirus) which can lead to phenocopies were investigated with negative results. Based on these and previous observations, it seems clear that a distinct form of autosomal recessive microcephaly associated with chorioretinal degeneration can be separated from the heterogeneous group of entities which presents microcephaly.

Oral‐facial‐digital syndrome with fibular aplasia: a new variant

Figuera LE, Rivas F, Cantú JM. Oral‐facial‐digital syndrome with fibular aplasia: a new variant.

Inherited hypertrichoses: Inherited hypertrichoses

Hypertrichosis is a rare condition characterized by excessive growth of hair (terminal, vellus or lanugo) in areas of the body that are not predominantly androgen dependent, and it is independent of age, race or sex. It can be congenital, late‐onset, generalized, localized, inherited or acquired. More than 50 different OMIM entries related to hypertrichosis exist, few of them with a localized gene locus or with a candidate gene. The review of generalized hypertrichoses from a historical point of view, including a review of their clinical and genetic features, shows heterogeneity with at least nine different entities. A short analysis of other forms of hypertrichosis is presented.

Red blood cell sorbitol dehydrogenase deficiency in a family with cataracts

SummarySorbitol dehydrogenase (SORD) was quantitatively assayed in a family in which four out of five brothers and their father had bilateral cataracts. Three sibs (two of them with cataracts) and both their father and paternal grandfather had SORD activity of about 25% of the reference values; of the other two affected sibs one had about 50% and the other had 75%; the mother and two paternal uncles had about 75%. These results do not define a clear cataract-SORD deficiency etiopathogenic relationship, nevertheless, they strongly suggest activity polymorphism in human red cell SORD, which would be highly relevant not only to the study of cataracts but of other major complications in diabetes.

G-6-PD Guadalajara. A new mutant associated with chronic nonspherocytic hemolytic anemia

SummaryThis paper describes a new G-6-PD variant designated Guadalajara, which was found in a Mexican boy suffering from chronic hemolytic anemia. The red cell enzyme activity of the subject is about 14%. The mutant enzyme showed rapid electrophoretic mobility, slightly increased affinity for glucose-6-phosphate, slightly decreased affinity for NADP+, moderately elevated utilization of substrate analogues, and normal heat stability, pH curve, and inhibition by NADPH. G-6-PD Guadalajara differs from all previously reported variants and is the first variant associated with chronic hemolysis found in Mexico.