A mutation in the pleckstrin homology (PH) domain of the FGD1 gene in an Italian family with faciogenital dysplasia (Aarskog-Scott syndrome).

Aarskog-Scott Syndrome (AAS) is an X-linked disorder characterised by short stature and multiple facial, limb and genital abnormalities. A gene, FGD1, altered in a patient with AAS phenotype, has been identified and found to encode a protein with homology to Rho/Rac guanine nucleotide exchange factors (Rho/Rac GEF). However, since this original report on identification of a mutated FGD1 gene in an AAS patient, no additional mutations in the FGD1 gene have been described. We analysed 13 independent patients with clinical diagnosis of AAS. One patient presented a mutation that results in a nucleotide change in exon 10 of the FGD1 gene (G2559>A) substituting a Gln for Arg in position 610. The mutation was found to segregate with the AAS phenotype in affected males and carrier females in the family of this patient. Interestingly, Arg-610 is located within one of the two pleckstrin homology (PH) domains of the FGD1 gene and it corresponds to a highly conserved residue which has been involved in InsP binding in PH domains of other proteins. The same residue is often mutated in the Bruton's tyrosine kinase (Btk) gene in patients with an X-linked agammaglobulinemia. The Arg610Gln mutation represents the first case of a mutation in the PH domain of the FGD1 gene and additional evidence that mutations in PH domains can be associated to human diseases.

Autosomal recessive familial exudative vitreoretinopathy: evidence for genetic heterogeneity.

Two unrelated families with familial exudative vitreoretinopathy (FEVR) show apparent autosomal recessive inheritance rather than the previously reported autosomal dominant or X-linked recessive mode of inheritance. Compared with the other modes of inheritance, the inherited clinical features here include earlier onset (at birth) and a more severe progressive course.

Phenotypic variability in the chromosome 9 ring.

The syndrome associated to the 9 ring is not commonly observed. The first remark was by Kistenmacher (1970) who examined a male. Later observation of other cases has allowed the syndrome to be described, so that it can be said to be characterized by constant signs, such as microcephaly, psychomotor retardation of varying entity and facial dysmorphism corresponding to that observed in 9 p monosomy. The variability of the phenotype has to be compared with the entity of the telomeric deletion, since the clinical outlook, especially the entity of retardation, could be less serious in case of small deletions.

Abnormal B.A.E.P. in a family with Moebius syndrome: evidence for supranuclear lesion.

A family with Moebius syndrome is presented. Neurological lesions in the affected members are various: complete VI and VII cranial nerves palsy associated with mental retardation in the proband; left convergent strabismus and mental retardation in a brother of the proband and only mental retardation in a sister of the proband. The brainstem auditory evoked potentials (B.A.E.P.), investigated in the proband and his affected sister, are abnormal. The presence of the anomaly after the 3rd wave is consistent with a disfunction of the auditory tract at a supranuclear level. The mental deficiency and the supranuclear site of the acoustic lesion are an indication for a more general involvement of C.N.S. than cranial nerve nuclei alone. Karyotype and dermatoglyphics of the three affected subjects were normal. The authors hypothesized the same disorganogenetic factor acting very early (4th-6th week of gestational age) on the metamerization process of limb buds mesoderm and brainstem gray matter.

Study of a form of pulverulent cataract in a large kindred.

A large kindred (64 members in four generations), affected by a form of apparently congenital pulverulent cataract, was studied for linkage of its gene locus with that of the Fy blood group. No indication of linkage was found. The involvement of the cortex distinguishes this form from the zonular pulverulent cataract (total nuclear) of Nettleship and Ogilvie, the locus of which is probably linked with Fy. A correlation between morphological and genetic heterogeneity, based on the linkage with Fy, cannot be established because of the scarcity of published data.

Multiple skeletal familial abnormalities associated with balanced reciprocal translocation 2;8(q32;p13).

A father and three of his offspring had skeletal abnormalities consisting of a short forearm, cubitus valgus, fusion of first and second cervical vertebrae, and cleft of L5 and S1. All four had a reciprocal, apparently balanced, translocation 2;8(q32;p13). Normal sibs had normal chromosomes. We conclude that this may be a rare instance of an autosomal dominant condition associated with a balanced chromosome translocation.

[Severe mental retardation and slight dysmorphism in a child with a bisatellite extrachromosome: inversion duplication (15)?]. / Grave ritardo mentale e lieve dismorfismo in bambino con extracromosoma bisatellite: inv dup (15)?

A de novo tetrasomy 15 has been reported, in a 6 years old child. The patient had severe mental retardation an minimal physical stigmata, consisting in slight skeletal and facial dismorphism. Cytogenetic analysis showed that extrachromosome, G-like long, was bisatellited and dicentric and was interpreted either as an inversion duplication 15 or as 15; G or D translocation.

[Aarskog's syndrome (facial-digital-genital syndrome). Study of a family (author's transl)]. / Sindrome di Aarskog (sindrome facio-digito-genitale). Studio di una famiglia.

A case of Aarskog syndrome in a 6-years old boy is reported. The patient showed clinical pictures typical of the syndrome: characteristic dysmorphic facies, palpebral ptosis, brachyfalangism, abnormality of the scrotum. Minimal stigmata and clinodactyly of 5th finger were present in a sister. Isolated bilateral clinodactyly was found in other 4 members of the family. The significance of this sign in the context of the syndrome has been discussed. Unusual dermatoglyphic patterns were present in the proband, mother and sister.

[XXXXY syndrome: clinical-radiological findings in one patient (author's transl)]. / Su una osservazione di sindrome XXXXY: rilievi clinico-radiologici.

A case of XXXXY syndrome in a 15 year old male is reported. Clinical findings (mental retardation, muscular hypotonia, hypogonadism, characteristic facies), chromosome analyses as well as fingerprint ridge counts were typical of the syndrome. Several radiological abnormalities were found. It is noteworthy that features consistent with epiphysial dysplasia were present. In the patient's kindred a case of "cri du chat" syndrome and a 5:9 balanced translocation were discovered.

A and B postaxial polydactyly in two members of the same family.

Two cases of previously unreported simultaneous presence of A and B postaxial polydactyly in two brothers out of 12 affected members of a kindred are reported. The findings are consistent with the hypothesis that in this family A and b types of postaxial polydactyly are caused by a single gene rather than by two different genes.