Spectrum of mutations in cystinuria patients presenting with prenatal hyperechoic colon.

Cystinuria is a heterogeneous, rare but important cause of inherited kidney stone disease due to mutations in 2 genes: SLC3A1 and SLC7A9. Antenatal hyperechoic colon (HEC) has been reported in some patients as a non-pathological consequence of the intestinal transport defect. We report 83 patients affected by cystinuria: 44 presented prenatally with a HEC (HEC group) and 39 with a classical postnatal form (CC group). SLC3A1 and SLC7A9 were sequenced. All patients were fully genotyped, and the relationship between the genotype and clinical features was analyzed. We identified mutations in SLC3A1 in 80% of the HEC group and in only 49% of the CC group. The SLC3A1 p.Thr216Met mutation was found in 21% of the alleles in the HEC group but was never found in the CC group. Most of the mutations found in the HEC group were considered severe mutations in contrast with the CC group. Twenty-five novel mutations were reported. This study shows a relationship between genotype and the clinical form of cystinuria, suggesting that only the patients with the most severe mutations presented with an HEC. These results emphasized the need for prenatal cystinuria screening using classical third-trimester ultrasound scan and the early management of suspected newborns.

Multiple congenital anomalies in two boys with mutation in HCFC1 and cobalamin disorder.

The cobalamin type C deficiency is a rare condition that results from impaired biosynthesis of both methylcobalamin (MeCbl) and adenosylcobalamin (AdoCbl). Hemizygous mutations of the HCFC1 gene explain the majority of clinically and biologically compatible cblC patients without MMACHC mutations (OMIM 309541). We report a family with two maternal half-brothers with multiple congenital anomalies and HCFC1 gene mutation in the second Kelch domain. Both presented with dysmorphic features (flat profile, cleft lip for one), increased nuchal translucency, prenatal onset microcephaly and hypospadias. Additionally to early onset intractable epilepsy and profound neurocognitive impairment, this familial observation suggests that HCFC1 gene should be considered in boys with midline malformations, even without proven cobalamin C deficiency.

[Intra- and interfamilial phenotype variation in Birt-Hogg-Dubé syndrome: Consequences for therapy]. / Variation phénotypique intra- et interfamiliale dans le syndrome de Birt-Hogg-Dubé : conséquences sur la prise en charge.

BACKGROUND: Birt-Hogg-Dubé syndrome (BHDS) is an autosomal-dominantly inherited genodermatosis that predisposes to the development of benign hair follicle tumours, lung cysts, kidney tumours, and possibly colonic cancers, due to mutations in the FLCN gene. We report cases involving a new mutation in three unrelated families. MATERIALS AND METHODS: Blood samples of three probands were submitted for a molecular diagnosis of BHDS. Following DNA extraction, FLCN gene sequencing was performed. The identified mutations were confirmed on a second sample. A cancer genetics consultation was organized and specific tests (dermatological examination, CT scan of chest and abdomen and colonoscopy) were proposed for each BHDS patient. RESULTS: FLCN gene-sequencing analysis revealed an identical complex harmful mutation in all three families. The first proband showed fibrofolliculomas (FF), a history of pneumothorax and colonic adenoma. The mutation was found in a brother and two sisters, who were asymptomatic, and in a niece with FF. The second proband showed FF. The mutation was found in her mother, who had FF. The third proband presented diffuse emphysema and very rare FF. DISCUSSION: This case report shows extremely wide intra- and interfamilial phenotype variation within individuals having a similar FLCN gene mutation. In large cohorts of BHDS patients, no genotype-phenotype correlation has been shown. This case emphasises the vital importance of presymptomatic diagnosis for each member of a BHDS family by means of a cancer genetics consultation, followed by a CT scan of the chest and abdomen, colonoscopy and annual kidney imaging.

Xeroderma pigmentosum group C in a French Caucasian patient with multiple melanoma and unusual long-term survival.

We report the case of an 83-year-old French woman with multiple melanomas showing a severe DNA repair deficiency, corrected after transfection by XPC cDNA. Two biallelic mutations in the XPC gene are reported: an inactivating frameshift mutation in exon 15 (c.2544delG, p.W848X) and a missense mutation in exon 11 (c.2108 C>T, P703L). We demonstrate that these new mutations are involved in the DNA repair deficiency and confirm the diagnosis of xeroderma pigmentosum from complementation group C (XP-C). We speculate that the coexistence of a MC1R variant may be involved in the phenotype of multiple melanomas and that the unusual long-term survival may be related to a lower ultraviolet radiation exposure and to a regular clinical follow-up. This patient appears to be the first French Caucasian XP-C case and one of the oldest living patients with XP reported worldwide.

[Value of ultrasonic diagnosis in the evaluation of hip dislocation in neonates and infants. Apropos of 340 cases]. / Valeur de l'échographie dans le bilan de la maladie luxante de la hanche du nouveau-né et du nourrisson. A propos de 340 cas.

Ultrasound imaging of hip (UIH) was performed in 170 children (340 hips) with normal (193) and dysplasic (147) hips and findings compared with results of clinical and radiologic examinations. Ultrasound demonstrated 100% sensitivity in cases with abnormal clinical and radiologic finding, and 94% specificity for UIH when clinical and radiologic examinations were negative. Sensitivity and specificity of ultrasound screening (respectively 96 and 81%) were comparatively superior to those of radiography of the pelvis (83 and 78%) in relation to the clinical examinations. These findings predict further development of UIH for screening of congenital dislocation of the hips and for follow up surveillance of treated children.