We describe five members of a consanguineous Pakistani family (Family I) plus two affected children from families of different ethnic origins presenting with neurodevelopmental disorders with overlapping features. All affected individuals from families have intellectual disability (ID), ranging from mild to profound, and reduced motor and cognitive skills plus variable features including short stature, microcephaly, developmental delay, hypotonia, dysarthria, deafness, visual problems, enuresis, encopresis, behavioural anomalies, delayed pubertal onset and facial dysmorphism. We first mapped the disease locus in the large family (Family I), and by exome sequencing identified homozygous ZNF407 c.2814_2816dup (p.Val939dup) in four affected members where DNA samples were available. By exome sequencing we detected homozygous c.2405G>T (p.Gly802Val) in the affected member of Family II and compound heterozygous variants c.2884C>G (p.Arg962Gly) and c.3642G>C (p.Lys1214Asn) in the affected member of Family III. Homozygous c.5054C>G (p.Ser1685Trp) has been reported in two brothers with an ID syndrome. Affected individuals we present did not exhibit synophrys, midface hypoplasia, kyphosis, 5th finger camptodactyly, short 4th metatarsals or limited knee mobility observed in the reported family.

我们描述了一个近亲的巴基斯坦家庭（家庭I）的五个成员，以及来自不同族裔家庭的两个受影响的儿童，这些儿童表现出具有重叠特征的神经发育障碍。所有受影响的家庭成员均患有智力障碍（ID），范围从轻度到深刻，并且运动和认知能力下降，加上各种特征，包括身材矮小，小头畸形，发育迟缓，肌张力低下，构音障碍，耳聋，视觉问题，遗尿症，遗尿症，行为举止异常，青春期延迟发作和面部畸形。我们首先在一个大家族（家族I）中绘制了该疾病的基因座，并通过外显子组测序确定了纯合子ZNF407c.2814_2816dup（p.Val939dup）在四个可获得DNA样本的受影响成员中。通过外显子组测序，我们在家族II的受影响成员中检测到纯合子c.2405G> T（p.Gly802Val），并在杂合子中检测到了杂合子变体c.2884C> G（p.Arg962Gly）和c.3642G> C（p.Lys1214Asn）。家庭III的受影响成员。据报道，有两个患有ID综合征的兄弟的纯合子c.5054C> G（p.Ser1685Trp）。在我们报告的家庭中，我们目前受影响的个体没有表现出滑膜，中面部发育不全，后凸畸形，第5指弯曲，第4 short骨短或膝盖活动受限。