Epilepsy and mental retardation limited to females: an X-linked dominant disorder with male sparing

Abstract

Several X-linked disorders affect females disproportionately or exclusively. These including focal dermal hypoplasia, oral-facial-digital syndrome type I (ref. 3) and epilepsy with bilateral periventricular heterotopias. X-linked dominant inheritance with male lethality is probably responsible for sex-limited expression of these disorders, as affected women have frequent spontaneous abortions and the sex ratio of their live offspring is often skewed. The same inheritance pattern has been proposed for Rett syndrome, Aicardi syndrome and microphthalmia with linear skin defects, but in these sporadic conditions, evidence of male lethality is lacking. We investigated an unusual family with epilepsy and mental retardation limited to females (EFMR, #121250 in ref. 9); this disorder is transmitted both by females and by completely unaffected carrier males. Assignment of the EFMR disease locus (EFMR) to the X chromosome indicates that selective involvement of females in X-linked disease may in some instances result from male sparing rather than male lethality.

Cloning and Functional Expression of a Human Na+and Cl−-dependent Neutral and Cationic Amino Acid Transporter B0+

“…The genomic sequences (GenBank accession numbers AL034411 and Z96810) were assigned to chromosome X at positions Xq24 and Xq22.1-23, respectively. Interestingly, several forms of nonspecific mental retardation and other central nervous system disorders have been mapped to this region (55)(56)(57)(58)(59)(60)(61)(62).…”

True hermaphroditism associated with microphthalmia

“…The ovotestis is the most common type of gonad in true hermaphroditism (2), constituting 44% of gonads in a survey of 409 cases reported up to 1981 (6). On the other hand, microphthalmia is an abnormality usually caused by interstitial deletion of chromosome 13, 18 or X, and rarely by an X-linked abnormality because X-linked disorders in males are not uncommonly a lethal disorder (7)(8)(9). Furthermore, the relationship between the deletion of the short arm of the X chromosome, abnormal sexual development, and the possible role of the short arm of the X chromosome locus involved in human sex determination has already been suggested (10).…”

Epilepsy Caused by Pcdh19 Gene Mutation: A Review of Literature and the Authors’ Observations

“…Мутации в гене PCDH19 (protocadherin 19), лока-лизованном на хромосоме Xq22, ассоциированы с эпилепсией и умственной отсталостью у пациентов женского пола [6,20].…”

“…«Эпилепсия с умственной отсталостью, ограни-ченной женским полом» была впервые описана в од-ной семье из Северной Америки в 3 последовательных научных сообщениях (R. C. Juberg и C. D. Hellman, 1971; K. Fabisiak и R. P. Erickson, 1990; S. G. Ryan et al, 1997) [11,19]. В нескольких поколениях этой семьи встречались больные женского пола с эпилепсией, начинающейся в младенческом возрасте, нормальным развитием до дебюта приступов и последующим рег-рессом развития с формированием умственной отста-лости различной степени тяжести.…”